Diabetic neuropathy is associated with significant impairments in bladder and erectile function. This Project will utilize a multidisciplinary approach to evaluate the contribution(s) of neural regulation and myocyte function to this process. In short, we will examine two main hypotheses. First, that neural regulation and myocyte ionic mechanisms (i.e., K channels, gap junctions and transmembrane Ca2+-flux) make organspecific contributions to bladder and erectile function. Second, that diabetic neuropathy is associated with quatifiable and organ-specific alterations in neural and myocyte function. Our Preliminary Data supports both suppositions. To this end, we will utilize the Streptozotocin (STZ)- and BB/W diabetic rat models. Bladder and corporal tissue will be obtained at monthly intervals ranging from 1-8 months on male STZ- and BB/W rats and their respective insulin-treated and age-matched control counterparts, and we shall: Specific Aim #2: Utilize organ bath techniques to evaluate the contribution of neural stimulation and myocyte ionic mechanisms to modulation of contraction and relaxation responses on isolated tissue strips. Specific Aim #2: Utilize sharp electrode recording techniques to evaluate the contribution of nascent and evoked neural stimulation and myocyte ionic mechanisms to electrical activity recorded in isolated tissue strips. Specific Aim #3: Utilize patch clamp techniques to evaluate the regulation and activity of K channels and transmembrane Ca2+-flux in freshly isolated myocytes. Specfici Aim #4: Utilize Fura-2 based digital imaging microscopy to evaluate the contribution of K channels and transmembrane Ca2+-flux to the modulation of cytosolic calcium levels, and contraction and relaxation of freshly isolated myocytes.